Anti-Inflammatory Effects of Concentrated Ethanol Extracts of Edelweiss (Leontopodium alpinum Cass.) Callus Cultures towards Human Keratinocytes and Endothelial Cells
Edelweiss (Leontopodium alpinum Cass.) is traditionally employed in folk medicine as an anti-inflammatory remedy. In nature, the plant is sparsely available and protected; therefore production of callus cultures was established. A concentrated ethanolic extract of culture homogenate, with leontopodic acid representing % of the total phenolic fraction (ECC55), was characterized for anti-inflammatory properties in primary human keratinocytes (PHKs) and endotheliocytes (HUVECs). Inflammatory responses were induced by UVA+UVB, lipopolysaccharide (LPS), oxidized low-density lipoprotein (oxLDL), and a mixture of proinflammatory cytokines. Trichostatin A, a sirtuin inhibitor, was used to induce keratinocyte inflammatory senescence. ECC55 (10–50？μg/mL) protected PHK from solar UV-driven damage, by enhancing early intracellular levels of nitric oxide, although not affecting UV-induced expression of inflammatory genes. Comparison of the dose-dependent inhibition of chemokine (IL-8, IP-10, MCP-1) and growth factor (GM-CSF) release from PHK activated by TNFα + IFNγ showed that leontopodic acid was mainly responsible for the inhibitory effects of ECC55. Sirtuin-inhibited cell cycle, proliferation, and apoptosis markers were restored by ECC55. The extract inhibited LPS-induced IL-6 and VCAM1 genes in HUVEC, as well as oxLDL-induced selective VCAM1 overexpression. Conclusion. Edelweiss cell cultures could be a valuable source of anti-inflammatory substances potentially applicable for chronic inflammatory skin diseases and bacterial and atherogenic inflammation. 1. Introduction Since ancient time, plants have been undiminished sources of products traditionally used for medicinal and skin care purposes. In our highly technological era, natural substances of plant origin remain major active principles of numerous drugs and “ceuticals” (nutraceuticals and cosmeceuticals). According to pharmacological statistics, 12 out of 40 anti-inflammatory drugs approved between 1983 and 1994 worldwide were derived from or based on secondary plant metabolites, mainly polyphenols [1]. Recently, a number of in vitro and in vivo animal studies have provided first scientific evidence for ethnopharmacological use of Leontopodium alpinum Cass. (family Asteraceae, named also Edelweiss) as a potent anti-inflammatory [2–5] and antibacterial remedy [6, 7]. Edelweiss is a famous plant sparsely distributed in high mountains of Europe and Asia at altitude of 1800–3000？m. The rare plant spontaneously grows in inaccessible areas, and it is protected in many countries [8]. In European folk medicine,
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